Preparation and characterization of a collagen/chitosan/heparin matrix for an implantable bioartificial liver

A new type of collagen/chitosan/heparin matrix, fabricated by gelation of collagen/chitosan with heparin sodium containing ammonia, was produced to construct livers by tissue engineering and regenerative engineering. The obtained collagen/chitosan/heparin matrix was found to be highly porous, swelled rapidly in PBS solution and was stable in vitro for at least 60 days in collagenase/lysozyme containing buffered aqueous solution (PBS, pH 7.4) at 37°C. The collagen/chitosan/heparin matrix resulted in a superior blood compatibility compared to the ammonia-treated collagen and collagen/chitosan matrices. The morphology and behavior of the cells on the collagen/chitosan/heparin membrane were found to be similar to those on the collagen membrane but different from those on the collagen/chitosan membrane. Hepatocytes cultured on the collagen/chitosan/heparin matrices exhibited highest urea and triglyceride secretion functions 25 days post seeding. These results suggest that this collagen/chitosan/heparin matrix is a potential candidate for liver tissue engineering.

[1]  V. Zecchi,et al.  Chitosan microcapsules as controlled release systems for insulin. , 1997, Journal of microencapsulation.

[2]  L G Griffith,et al.  Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels. , 1998, Annals of surgery.

[3]  I. Gouda,et al.  Heparin-chitosan complexes stimulate wound healing in human skin. , 1997, Scandinavian journal of plastic and reconstructive surgery and hand surgery.

[4]  J. Vincent,et al.  Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. , 1997, Chest.

[5]  E. Edelman,et al.  Perivascular graft heparin delivery using biodegradable polymer wraps. , 2000, Biomaterials.

[6]  G. Hill Cardiopulmonary bypass-induced inflammation: is it important? , 1998, Journal of cardiothoracic and vascular anesthesia.

[7]  D. Heimbach,et al.  Artificial Dermis for Major Burns: A Multi‐Center Randomized Clinical Trial , 1988, Annals of surgery.

[8]  J. Folkman,et al.  Control of angiogenesis by heparin and other sulfated polysaccharides. , 1992, Advances in experimental medicine and biology.

[9]  H P Wendel,et al.  Coating-techniques to improve the hemocompatibility of artificial devices used for extracorporeal circulation. , 1999, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[10]  R. Kronenthal,et al.  Medical and surgical applications of collagen. , 1973, International review of connective tissue research.

[11]  Alina Sionkowska,et al.  Effect of UV radiation on the infrared spectra of collagen , 1996 .

[12]  John A. Frangos,et al.  Physical forces and the mammalian cell , 1993 .

[13]  M. Morimoto,et al.  Effects of chitin/chitosan and their oligomers/monomers on migrations of fibroblasts and vascular endothelium. , 2002, Biomaterials.

[14]  W. J. Wang,et al.  Crosslinked collagen/chitosan matrix for artificial livers. , 2003, Biomaterials.

[15]  R Langer,et al.  Long-term engraftment of hepatocytes transplanted on biodegradable polymer sponges. , 1997, Journal of biomedical materials research.